Gao

etal. J Nanobiotechnol (2021) 19:96

https://doi.org/10.1186/s12951-021-00825-4

REVIEW

Biomedical applications of2D

monoelemental materials formed bygroup VA

andVIA: aconcise review

Ping Gao

1†

, Yufen Xiao

2†

, YuliangWang

, Leijiao Li

, Wenliang Li

and Wei Tao

Abstract

The development of two-dimensional (2D) monoelemental nanomaterials (Xenes) for biomedical applications has

generated intensive interest over these years. In this paper, the biomedical applications using Xene-based 2D nano-

materials formed by group VA (e.g., BP, As, Sb, Bi) and VIA (e.g., Se, Te) are elaborated. These 2D Xene-based theranostic

nanoplatforms confer some advantages over conventional nanoparticle-based systems, including better photother-

mal conversion, excellent electrical conductivity, and large surface area. Their versatile and remarkable features allow

their implementation for bioimaging and theranostic purposes. This concise review is focused on the current devel-

opments in 2D Xenes formed by Group VA and VIA, covering the synthetic methods and various biomedical applica-

tions. Lastly, the challenges and future perspectives of 2D Xenes are provided to help us better exploit their excellent

performance and use them in practice.

Keywords: 2D materials, Monoelemental, Group VA and VIA, Biomedical applications

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Background

Two-dimensional (2D) materials are one of the emerg-

ing materials, which have more than 100nm or even sev-

eral microns with one or a few atomic thicknesses [1]. In

2004, Novoselov and Geim adopted the mechanical sepa

ration method to obtain graphene [2]. Graphene is a kind

of two-dimensional material with hexagonal honeycomb

shape formed by sp

hybridization of carbon protons [3].

Due to its excellent electrical conductivity, high thermal

conduct covering sensors, transistors, new energy bat

teries, hydrogen storage materials, aerospace and so on

[4–6]. e great success of graphene has led to a remark

able boom in the development of 2D nanomaterials, such

as transition metal dihalide (TMD), nitrides and car

bonitrides (MXenes), hexagonal boron nitride (h-BN),

graphite phase nitrogen carbide (g-C

), molybdenum

disulﬁde(MoS

), layered rare earth hydroxide (LRH), lay-

ered double hydride (LDH) and their derivatives [7–10].

2D nanomaterials with ultrathin lamellate nanostructure

exhibit weak interlayer bonding and strong covalent in-

plane bonding [11]. ere are multifarious unique prop

erties of 2D nanomaterials including the large surface

area, the improved chemical and physical reactivities

[12–14]. Particularly, the dramatically increased surface

area of 2D nanomaterials aﬀects a 2D wave function due

to the quantum conﬁnement eﬀects. Consequently, 2D

nanomaterials are characterized by impressive photonic

[15], catalytic [16], magnetic [17], and electronic proper

ties [18] that diﬀer from those of the bulk counterparts,

resulting in a wide-ranging application.

In recent years, 2D monoelemental nanomateri

als (Xenes) based on group VA and VIA have gradu-

ally entered the researchers’ ﬁeld of vision, which is

Open Access

Journal of Nanobiotechnology

*Correspondence: lileijiao@cust.edu.cn; wenliangl@ciac.ac.cn

†

Ping Gao and Yufen Xiao contributed equally to this work

School of Chemistry and Environmental Engineering, Changchun

University of Science and Technology, Changchun 130022, China

Jilin Collaborative Innovation Center for Antibody Engineering, Jilin

Medical University, Jilin 132013, China

Full list of author information is available at the end of the article

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Gaoetal. J Nanobiotechnol (2021) 19:96

encouraged by the dramatically development of phos-

phorene (black phosphorus, BP) [19–22]. Due to the

excellent optical and electronic properties, Xenes have

been considered to be promising biological theranos

tic agents to address various challenges in healthcare

[23–30]. Xenes can be used as diagnosis agents for com

puted tomography (CT), photoacoustic imaging (PAI),

ﬂuorescence imaging (FI), etc. [31–34]. Moreover, Xenes

are employed in disease phototherapy, such as photo

thermal therapy (PTT) and photodynamic therapy (PDT)

against tumor, bacteria and virus [35–41]. e large sur

face area of Xenes endows them an incomparable high

loading capacity of therapeutic and/or ﬂuorescent mole

cules compared with traditional nanoparticle-based drug

delivery platforms. Besides, Xenes also could construct

biosensors with the attachment of various biological

markers like DNA, etc. [42, 43]. is paper reviews the

applications of Xenes formed by Group VA and VIA in

biomedical ﬁelds. To start with, the synthesis and physi

cal–chemical properties of Xenes are introduced. And

then their research progress in biomedicine ﬁelds were

summarized such as bioimaging, therapy and antibac

terial. Finally, on the basis of summarizing the current

situation, the paper puts forward the challenges and

prospects for future development of Xenes in group VIA

and VA (Fig.1).

Synthesis ofXenes

e synthetic methods of 2D Xenes can be categorized as

top-down fabrication and bottom-up synthesis (Table1).

e top-down method mainly uses mechanical force or

molecular intercalation to destroy interlayer bonding,

so as to strip the block and obtain a single or multi-layer

nanometer sheets [44]. e bottom-up approach is to use

chemical conversion methods to directly react diﬀerent

molecular precursors to form nanosheets [45, 46].

Top‑down

e top-down method mainly includes solid-phase strip-

ping and liquid-phase stripping. e solid phase stripping

refers to mechanical dissociation stripping. e liquid-

phase stripping relies on ultrasonic exfoliation, electro

chemical stripping, plasma-assisted process and so on.

Mechanical cleavage

Mechanical cleavage is an original and basic approach

to strip large layered materials into single or several lay

ers of nanometer sheets by mechanical forces using

transparent tape [47]. In recent years, researchers have

Fig. 1 Schematic illustration of the main topics covered in this

review

Table 1 Summary of Xene synthesis method

Periodic

Table

group

Element 2D form Morphology Synthesis methods Refs

VA P Phosphorene Nanosheets and quantum dots Mechanical cleavage, ultrasonic exfoliation,

electrochemical stripping, plasma-

assisted process Other top-down meth-

ods, MBE,CVD, Solvent-thermal method

[48–52, 65, 68, 71, 72, 74, 80, 86, 87]

VA As Arsenene Nanosheets and Nanodots Ultrasonic exfoliation, electrochemical

stripping, plasma-assisted process, Other

top-down methods

[55, 62, 69, 73]

VA Sb Antimonene Nanosheets and quantum dots Mechanical cleavage, ultrasonic exfoliation,

electrochemical stripping, plasma-

assisted process, Other top-down meth-

ods, MBE, Vander Waals extension

[26, 50, 56, 67, 70, 73, 75, 89]

VA Bi Bismuthene Nanosheets and quantum dots Ultrasonic exfoliation, Other top-down

methods, MBE, Wet chemistry

[57, 73, 78, 90]

VIA Se Selenene Nanosheets Ultrasonic exfoliation [58]

VIA Te Tellurene Nanosheets and quantum dots Ultrasonic exfoliation, MBE, Solvent-ther-

mal method, thermal evaporation

[59, 79, 88, 91]

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Gaoetal. J Nanobiotechnol (2021) 19:96

prepared many 2D nanomaterials by this method. In

2014, BP nanoﬂakes were ﬁrstly obtained by repeatedly

peeling the block crystal with transparent tape on Si/

SiO

substrate [48, 49]. e BP generated by the method

is easy to oxidize in the environment forming irreversible

phosphorus oxide compounds. erefore, it is necessary

to use inert gas or vacuum in the preparation process

to obtain pure BP nanosheets (Fig. 2a, b). In addition,

submillimeter-sized antimonene is prepared directly on

the SiO

/Si substrate by repeatedly tearing a block crys-

tal over the tape. However, the production yield based on

SiO

/Si substrate is very low. In 2016, Pablo Ares etal.

developed an improved method with the aid of viscoelas

tic polymer on the surface of SiO

substrate. As shown

in Fig.2c–h, the results of high resolution transmission

electron microscopy (TEM) and atomic force microscope

Fig. 2 a, b Crystal structure of few-layer phosphorene. a Perspective side view of few-layer phosphorene. b Side and top views of few-layer

millimeter-size crystals of antimony. Middle right, adhesive tape with sub-millimeter crystals of antimony. Bottom left, polymer on glass slide with

micrometer antimony ﬂakes. d Optical microscopy image where up to three large ﬂakes of antimony can be seen. e AFM topographic image

showing two ﬂakes of anti-monene located inside the marked region in d. f AFM topography of the ≈ 0.2 μm2 antimonene ﬂake inside the blue

square in e showing terraces of diﬀerent heights. g High-resolution TEM image of a few-layer antimonene ﬂake. The inset is a digital magniﬁcation

of the area inside the blue rectangle. h AFM topography acquired on the bilayer terrace marked with a green arrow in f showing atomic periodicity.

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Gaoetal. J Nanobiotechnol (2021) 19:96

(AFM) proved the excellent stability of antimonene pre-

pared by the improved method. And the theoretical cal-

culations of the antimony monolayer also proved the

inactive character with water and oxygen [50]. Although

mechanical cleavage is an easy and low-cost approach,

the yield is relatively low and the controllability and

repeatability are dissatisfactory.

Ultrasonic exfoliation

Recently, ultrasonic assisted liquid phase stripping has

attracted dramatically increasing attention. e bulk

layered crystal is ﬁrstly dispersed in designated medium

such as N-cyclohexyl-2-pyrrolidone (CHP), dimethyl

formamide (DMF), dimethylsulfoxide (DMSO), isopro-

pyl alcohol (IPA), N-methyl-pyrrolidone (NMP) and

so on [51]. With the help of ultrasonic wave, abundant

bubbles are generated on the surface of crystal through

hydroxyl radical mediating or pyrolysis reaction dur

ing ultrasonic cavitation and thus ultrathin 2D nanoma-

terials are produced ﬁnally. High-quality, uniform size,

low-layer BP nanosheets were prepared with ultrasonic

probe by liquid-phase exfoliation in both CHP and NMP

solution under cooling condition (Fig. 3a, b) [52, 53].

Furthermore, Song et al. produced BP quantum dots

(QDs) by liquid-phase exfoliation with ultrasonic probe

in NMP by tuning power and reaction time (Fig.3c) [54].

ese BP QDs possess the average size of 3.5–4.5 nm

and the thickness of 1.2–1.6nm with the lattice fringes

of 0.26nm and 0.32nm assigned to the (004) and (012)

plane of BP. Coincidentally, arsenene (2D arsenic) has

also been prepared using gray arsenic as raw material

by liquid-phase exfoliation in NMP. As shown in Fig.3d,

e, the thickness of the prepared arsenic ﬂakes is 6–12

atomic layers and the size is 100–350nm in average. e

Raman spectra showed thickness dependence. None

theless, the products are only arsenic nanoparticles by

replacing solvent medium with toluene when other con

ditions are held constant [55]. e lamellar β-antimonene

was obtained by ultrasonication in a mixture of IPA and

water (IPA:water = 4:1) at 400 W for 40 min (Fig. 3f).

e transverse size is greater than 1-3μm

accompanied

with the thicknesses 4 nm [56]. Tao et al. synthesized

the ultra-small and uniform size antimony quantum

dots by the two-step combined ultrasonic strategy of

ultrasound probe sonication and ice bath ultrasound in

ethanol, and modiﬁed them with 1,2-Distearoyl-sn-glyc

ero-3-phosphoethanolamine-N-[methoxy (poly ethylene

glycol)] (DSPE-mPEG) to improve their dispersion and

stability in physiological media. As presented in Fig.3g,

h, the average size of the exposed antimony quantum

dots is approximately 2.8nm, and the average thickness

is approximately 1.6nm. e average size of antimony

quantum dots modiﬁed by mPEG is 3.9nm and the aver

age thickness is 2.6nm [26].

Ultrathin bismuthene QDs can be produced by liquid-

phase exfoliation in NMP for 48h under the power of

400W (Fig. 3i) [57]. Selenene (2D selenium) has been

experimentally obtained with 200W power liquid-phase

exfoliation along with 360W ultrasound treatment sub

sequently. As shown in Fig. 3k, the obtained selenium

nanosheets with the size of 20–130nm and the thickness

of less than 10nm have been successfully applied in pho

toelectric ﬁelds [58]. Tellurene (2D Tellurium) could also

be obtained by liquid-phase exfoliation in IPA after pul

verizing. e prepared 2D Te nanosheets with good sta-

bility keep the crystallization characteristics during the

stripping process (Fig. 3l) [59]. For size/thickness-con

trollable preparation of 2D Xenes by ultrasound-assisted

liquid phase exfoliation, the decisive factor should be the

power and the reaction time of ultrasonic. And the ﬁrst

critical factor should be the appropriate selection of sol

vent. e above mentioned organic solvent molecules

could be embedded into the interlayer of layered mate

rials like wedges, which is beneﬁcial to break the weak

van der Waals forces and gain ultrathin nano-lamina.

e decisive factor should be the power and the reaction

time of ultrasonicto size/thickness-controllable prepara

tion of 2D Xenes [60–62]. Ultrasonic exfoliation is one of

Fig. 3 a Basic characterization of exfoliated black phosphorous (CHP as solvent, scale bars 100 μm, 500 nm and 1 nm). Reprinted with permission

Schematic of the preparation of arsenenenanosheets in NMP and nanodots in toluene from grey arsenic. Reprinted with permission [55], Copyright

2018 Royal Society of Chemistry. e Experimental morphological (TEM and AFM) images of arsenenenanosheets and nanodots. Reprinted with

bulk antimony, antimony powder, AMQDs solution during the preparation, process, TEM and AFM image of AMQDs. Reprinted with permission

(See ﬁgure on next page.)

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Gaoetal. J Nanobiotechnol (2021) 19:96

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Gaoetal. J Nanobiotechnol (2021) 19:96

the most eﬀective methods for preparing 2D Xenes, and

it is also considered as a universal method for various 2D

Xenes.

Electrochemical stripping

Electrochemical stripping including ion intercalation

method and anodizing method has been used in the syn

thesis of graphene. Recently, 2D Xenes were also obtained

with the assistance of mild ultrasound by ion intercala

tion method. e embedding cations (such as K

, Na

, etc.) could enlarge the space and weaken the van

der Waals force between layers. Besides, these cations

could also react with water to generate hydrogen, which

is beneﬁcial to the separation between layers as well and

thus improves the productivity [63, 64]. For instance, BP

nanosheets were successfully prepared from black phos

phorus ﬁlm by ion intercalation method. As illustrated in

Fig.4a–d, Adriano Ambrosi etal. used black phosphorus

ﬁlm as anode, platinum plate as cathode, and connected

with copper strip and put it into H

solution at given

voltage. e solution gradually turned yellow/orange

and ﬁnally turned deep orange. After cleaning and vac

uum drying, the small particles at the bottom were re-

dispersed in dimethylformamide (DMF). e green/gray

dispersion was obtained by ultrasonic treatment, and BP

nanosheets were obtained after vacuum drying at 40 ℃

[65].

e preparation of arsenene (2D arsenic) was achieved

by electrochemical stripping. Bulk arsenic was used as

cathode (working electrode), platinum and Ag/AgNO

were used as anode and reference electrode, respec

tively. In this reaction, ammonium hexaﬂuorophosphate

(NH

) was selected as electrolyte and then accumu-

lated on the surface of anode (Fig.4e). e multilayered

arsenic pieces further screen out 2D arsenene with thick

ness of 0.6nm. is electrochemical assisted method will

facilitate the application of arsenene in a new genera

tion of electronic devices [66]. Using platinum and anti-

mony as electrodes in Na

and Li

electrolytes

at 5V for 2h to obtain antimonene (2D antimony) [67].

e voltage polarity and the type of electrolyte have an

important inﬂuence on the peeling production (Fig.4f).

Electrochemical stripping is a scalable method to obtain

biocompatible Xenes. Compared with the traditional

method, this method can prepare high yield and low cost

2D materials with high requirements, which have been

realized in phosphorene, MoS

and other materials.

Plasma assisted process

is method is important for the fabrication of high-

performance phosphenyl nanoelectronic devices.

Phosphorene could be prepared by pyrolysis of black

phosphorus crystal on SiO

/Si substrate using Ar

plasma (13.56 MHz RF source), 30 pair pressure and

30 W power at room temperature. According to the

Raman spectra, the frequency of A

mode becomes hard

with the decrease of atomic thickness, while the frequen

cies of β

and A

modules are almost constant. is may

be due to the anisotropic structure changes of diﬀerent

thickness of phosphoranes [68].

Moreover, Tsai et al. synthesized multilayer arse

nic nanosheets using plasma-assisted processes on the

InAs substrate (Fig.5a, b) [69]. ere are many factors

that aﬀect the size, thickness and morphology of arse

nic nanosheets including annealing time and the plasma

exposure time. e greater the plasma power, the higher

the arsenic phonon mode strength and the more crystal

defects. e heterostructure includes multilayered arse

nic, InN and InAs substrates, respectively. e multilayer

antimony nanoribbons can be prepared by immersing the

InSb substrate in a 50–200W N

plasma for 30–60min

at 10

−1

 torr and then drying and annealing in N

(10/1, V/V) atmosphere for 30–60min (Fig.5c, d) [70].

However, this method is suitable for mass production of

2D nanomaterials due to its high cost and high equip

ment requirements.

Other top‑down methods

In addition to the above-mentioned preparation methods

of 2D Xenes, there are many other preparation meth

ods. Xu etal. mixed large black phosphorus crystals with

NMP in a 1:1 ratio (weight ratio w/w) under vigorous stir

ring by a household mixer for 40min at 250W power to

produce a single layer or several layers of BP nanosheets

[71]. A simple and eﬃcient microwave-assisted liquid-

phase stripping method was performed to prepare BP

nanosheets [72]. A large amount of black phosphorus

was dissolved in a small amount of NMP and heated in

a 600W microwave system at 50°C for 20–40min. And

then the intermediate products were transferred to a

(See ﬁgure on next page.)

Fig. 4 a Schematic of the black phosphorus exfoliation procedure. Snapshot of the electrochemical setup with BP ﬂake anode and Pt foil cathode

separated in acidic solution (0.5 M H

) by a ﬁxed distance of 2 cm at b no potential applied, c after 20 min applying a voltage of + 3 V and d

electrochemical exfoliation of native As toward (mono)few-layer arsenene: (blue dots) cations (NH4+); (red dots) anions (PF6−). Reprinted with

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Gaoetal. J Nanobiotechnol (2021) 19:96

220W microwave system at 70 ℃ for 3min to obtain a

dispersion of stable BP nanosheets. In addition, by using

hepatocholic acid as surfactant, the As, Sb and Bi bulk

crystals were dispersed and stirred acutely in the kitchen

mixer for 2h to obtain 2D As, Sb and Bi nanosheets [73].

TEM images showed that arsenic formed the largest thin

section with folded structure due to its high anisotropy,

and the layered structure was small. e thicknesses of

the synthetic 2D antimony was 10 times less than that

of 2D arsenic. e electronic transfer ability, sensing

performance and electrochemical performance of these

materials were measured.

Bottom‑up

e bottom-up method can be divided into physical

preparation, chemical preparation and other bottom-up

methods. Physical preparation includes molecular beam

epitaxy (MBE) in physical vapor deposition, and chemical

preparation includes chemical vapor deposition (CVD),

hydrothermal method and solvothermal method.

Molecular beam epitaxial

MBE is a vacuum coating technology in the synthesis of

modern semiconductor device materials. e thickness,

crystal orientation and doping amount of Xenes can be

accurately controlled by this method. For instance, using

black phosphorus as the precursor, P

molecules were

condensed from the vapor phase on the surface of Au

(111) substrate. After deposition and annealing, mon

olayer phosphorus with regular hexagonal morphology

was formed [74]. As shown in Fig.6a, high resolution

scanning tunnelling microscopy (HRSTM) showed that

the single phosphorus layer was highly ordered, and

each dark center was surrounded by six triangles. e

average distance between dark centers was about 14.7Å.

e measured electronic band gap of a single layer of

was about 1.10eV, which indicated that it was a new

kind of two-dimensional semiconductor material. It was

consistent with the theoretical predictions reported by

Zhu etal. e DFT calculations predicted the new form

of 2D phosphorus with a ﬂat "zigzag ridge", which was

Fig. 5 a TEM image of the multilayer arsenene/InN/InAs. (Inset:diﬀraction pattern of multilayer arsenene). b Thetheoretical atomic model of

multilayer antimonene/InN/InSb. d The theoretical atomic model of multilayer antimonene/InN/InSb layer structure.Reprinted with permission [70],

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Gaoetal. J Nanobiotechnol (2021) 19:96

similar to that of silene with layered honeycomb struc-

ture. 2D antimony was also obtained by MBE method

besides 2D phosphorus. Monolayer antimonene with

regular orientation and order array could grow on a

chemical stable layered TMD substrate (PdTe

) [75]. e

small mismatch (less than 2.3%) of the surface lattice

constant between the substrate (PdTe

, 4.01Å) and that

of free-standing antimonene (4.01Å) should be a criti

cal factor for the formation of the 2D antimony ﬁlm. e

resultant antimony membrane with honeycomb lattices

is similar to graphene is highly ordered and symmetric.

e height of antimony coating was 2.8 Å, which was

close to the calculated height of monolayer of antimony

(3.38Å) (Fig.6b).

e large band gap of 2D monolayer antimony indi

cated the potential applications for electronic and pho-

toelectric devices. Silicon is identiﬁed as a suitable

alternative substrate to prepare Xenes by MBE method

[76, 77]. For example, full-wafer monocrystalline bismuth

ﬁlms with the thickness within the range of 4 ~ 50 nm

have been grown on Si (111) substrates by MBE (Fig.6c)

[78]. Si (111) substrate was ﬁrstly soaked with dilute

hydroﬂuoric acid to remove the natural oxide and then

the substrate was loaded into a high vacuum and baked

at high temperature within 20 min to prevent second

ary oxidation. Bismuthene grows at a rate of 0.2Å/s at

room temperature observed by TEM. Bismuthene pos

sesses good 2D topological structure due to its quantum

Fig. 6 a Atomic model of blue phosphorus and experimental morphological (STM) images of phosphorus. Reprinted with permission [74],

an atomically ﬂat terraces separated by steps of height of ~ 4 Å. (The inset presents a line proﬁle taken along the white line drawn in the image).

Right: Atomic resolution STM image (size 8 × 8 nm2, bias: 0.6 V) showing rectangular lattices as highlighted by the black rectangle. Reprinted with

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size eﬀect, low carrier density and spin coupling eﬀect.

As for Group VIA, tellurene (2D tellurium) was recently

grown on both graphene/6H-SiC (001) and high orien

tation pyrolysis graphene (HOPG) using MBE technol-

ogy [79]. As shown in Fig.6d, the lattice of tellurene is

rectangular and the surface lattice constant is consistent

with the theoretical lattice constant. e tellurium thin

ﬁlms feature semiconductor characters, and the band gap

decreases with the increase of thickness. MBE method

could control the growth of Xenes at atomic scale due to

the slow deposition rate, however, the diﬃcult operation

limits their more applications.

Chemical Vapor Deposition (CVD)

CVD technology has gradually become an important

route for synthetic of uniform 2D inorganic materials.

BP thin ﬁlms with an average area of above 3 μm

were

prepared from red phosphorus successfully with insitu

chemical vapor deposition method [80]. e ﬁlm was

composed of four phosphorus atomic layers. In recent

years, many new 2D nanomaterials have been prepared

by CVD technology. e controllable growth of Sb

nanosheets occurs on the surface of SiO

[81]. Bismuth

oxide monocrystalline ﬁlms could be prepared on amor

phous substrates by aerogel-assisted CVD [82]. Chang

etal. used CVD technology to prepare continuous InSe

ﬁlms possessing high stability against oxidation [83].

CVD technology has many advantages in the prepara

tion of two-dimensional materials. e deposition rate

can be controlled by adjusting the process parameters,

such as gas pressure, gas velocity, temperature rising rate

and heat preservation time. CVD technology is simple

and relatively low in cost, which is suitable for large-scale

production and wide applications [84, 85].

Solvent‑thermal method

Solvent-thermal method is a common method to syn-

thesize nanomaterials. An impressive body of literature

indicates that solvent-thermal approach is a reliable

method for the synthesis of BP nanosheets. For instance,

high yield of BP nanosheets (30%) was prepared at 400

℃ (Fig. 7a) [86]. After vacuum drying, the uniform

2D nanocrystals with the transverse size of 1 μm and

the thickness of 0.5–4 nm were obtained, which was

characterized by less than 8 layers of black phosphorus

atoms (Fig. 7b–d). e lattice fringes of 0.27 nm and

0.23nm were on the (040) and (002) planes of orthogo

nal BP. e resultant BP nanosheets feature excellent

electrochemical properties as the positive electrode of

lithium ion battery. Tian etal. [87] took white phospho

rus as raw material and ethylenediamine as solvent to

obtain BP nanosheets with a few atomic layers through

solvent-thermal approach (Fig.7e–h). More interestingly,

the higher the solvothermal reaction temperature (in

60–140℃ range), the higher the yield of BP production.

e thickness of the synthetic BP nanosheets was within

the scope of 1–15 nm, which was comprised of 2–28

atomic layers. It was conducive to the expansion of BP

application scope in the ﬁeld of optoelectronic devices.

As for tellurium, sodium tellurite (Na

TeO

) is a

common tellurium source with hydrazine hydrate

•H

O) as the reducing agent for the preparation

of 2D tellurium by solvent-thermal approach [88]. As

shown in Fig.7i–k, the measurements of TEM and AFM

consistently demonstrated that the uniform dimensions

(about 15 μm) with the thickness of 10–30 nm of tel

lurene can be achieved by this process. e result indi-

cated that Te nanosheets were continuous lattices with a

lattice constant of 2Å corresponding to the (003) plane

of Te. Moreover, the thickness of 2D tellurium nanocrys

tals could be adjusted from single molecule membrane to

10nm by controlling reaction conditions. e resultant

2D tellurium nanosheets have high stability. In conclu

sion, the yield and morphology of 2D nanocrystals are

dramatically inﬂuenced by reaction temperature, raw

materials, solvents, and surfactants in this process.

Other bottom‑up methods

In order to obtain 2D materials with high crystallinity by

CVD technology, the perfect match in symmetry and lat

tice constants between the epitaxial layer and substrate is

a key index. Van der Waals epitaxy technology is recently

proposed to seed the epitaxial growth of 2D materials

on the substrate without suspended bond to avoid the

above restrictions. Ten atomic layered antimonene was

obtained by van der Waals epitaxy from antimony poly

hedrons on a bare (001) plane ﬂuorochemical substrate

(KMg

(AlSi

). e antimony vapor in the heat was

Figure7 a The morphology evolution of the bulk red phosphorus materials during the high-temperature solvothermal reaction. b

image of phosphorus-based nanosheets, showing the amorphous regions with some polycrystalline structure. d AFM image. e Synthetic protocol

of the black phosphorus. f TEM image of the BP nanosheets. g HRTEM image corresponding to F. Lattice Image of a BP ﬂake shows d spacing of the

Corresponding HR-TEM image. k AFM image of typical tellurium nanoﬂake (top) and the corresponding height proﬁle (bottom), scale bar is 1 µm.

(See ﬁgure on next page.)

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Gaoetal. J Nanobiotechnol (2021) 19:96

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Gaoetal. J Nanobiotechnol (2021) 19:96

transported downstream with Ar/H

mixed gas result-

ing in thin antimonene ﬁlms with less than 4nm [89].

Wet chemistry is another common bottom-up method

to prepare Xenes. Bismuthene was synthesized by this

method. e black sediment was obtained from the mix

ture of Bi(NO)

·5H

O, added water, ethylene glycol and

hydrazine hydrate (volume ratio 6:3:1) under vigorous

stirring it at 80 ℃ for 8h [90]. More recently, Zhao etal.

[91] deposited ultrathin tellurium ﬁlms by thermal evap

oration at low temperature (−80℃) when the pressure

reached 2 × 10

–6

mbar. Tellurium thin ﬁlm prepared by

this method has high Hall mobility and is a kind of high

performance p-type ﬁeld eﬀect transistors (FET) mate

rials with good switching characteristics. It has a broad

application prospect in electronic devices and mono

lithic 3D circuits. Tan etal. also reported the use of low

temperature (−110°C) thermal evaporation to prepare

1-x

thin ﬁlms with continuous adjustable band gap

from 0.31eV (Te) to 1.87eV (Se) [92]. e ﬁlms have

great application potential in the manufacture of low

cost, high performance, high resolution short-wave infra

red (SWIR) photodetectors and imaging sensors.

Application ofXenes inbiomedicine

erapeutic applications of 2D Xenes have witnessed

rapid growth for biomedical applications in recent

years. Because of their outstanding physical, chemical,

electronic and optical properties, 2D Xenes have been

explored in a variety of biomedical applications, such as

bioimaging, photothermal therapy (PTT), photodynamic

therapy (PDT), chemotherapy and antibacterial. ese

various adopted strategies in biomedical applications are

described as follows.

Bioimaging

Multimode imaging is paramount importance for the

identiﬁcation and diagnosis of the disease. It is a routine

technique to visualize morphological details in cells and

tissues to avoid unnecessary biopsies and reduce patient

suﬀering [93]. In this section, we will discuss the applica

tions of 2D Xenes in ﬂuorescence imaging (FI), photoa-

coustic imaging (PAI), and X-ray computed tomography

(CT) imaging.

FI is the visualization of ﬂuorescent dyes or proteins as

labels for molecular processes or structures. FI is a com

mon biological imaging model to achieve observations

including the location and dynamics of gene or protein

expression and molecular interactions in cells and tis

sues. 2D Xenes with ultra-high speciﬁc surface area can

eﬃciently load ﬂuorescent dyes for ﬂuorescence imag

ing. BP has been widely demonstrated as an excellent

ﬂuorescent dye delivery platform to achieve the require

ment of real-time imaging for living tissue. For example,

the modiﬁed nile blue dye (NB) was covalently modi

ﬁed BP nanosheets to form NB@BP, which could label

MCF-7 tumor sites with red ﬂuorescence and achieve

eﬀective tumor ablation under near-infrared irradiation

(Fig.8a) [94]. Fluoresce in isothiocyanate (FITC)-labelled

PEG-BP NSs has been demonstrated that it could enter

HeLa cells through cavity-dependent endocytosis and

macroendocytosis [95]. is result provides an available

evidence for deep investigating the transport mecha

nism and distribution of BP in cells. PEGylated BP load-

ing Cy7 could achieve a good accumulation in the tumor

sites model resulting invivo imaging [21]. BP quantum

dots have good biocompatibility, low toxicity, spontane

ous degradation analogous to BP nanosheets, especially

intrinsic ﬂuorescence properties making it a broad appli

cation prospect in bioimaging. Lee etal. found that black

phosphor quantum dots emitted blue ﬂuorescence in

HeLa cells under UV irradiation and green ﬂuorescence

under visible light irradiation (Fig.8a) [96]. Additionally,

antimonene has also been explored in ﬂuorescence imag

ing ﬁeld showing good accumulation and retention in the

mouse model of breast cancer cell inoculation (Fig.8b)

[27]. Cy5.5-labeled PEGylated antimonene nanosheets

were absorbed into MCF-7 cells by mass endocytosis and

cave-independent endocytosis, and then transported by

early endocyt-late endocyt-lysosome pathway.

PAI, which is based on the photoacoustic eﬀect, is an

emerging diagnostic modality to achieve the detection

of laser-irradiated tissue-induced pressure waves. PAI

has been applied to the imaging of cancer, wound heal

ing, disorders in the brain, and gene expression, among

others. Due to the thickness-dependent quantum size

eﬀect and adjustable crystal structure of Xenes, it is an

extremely attractive PAI reagent to achieve the sectional

or three-dimensional images of tissues and organs. For

example, PEGylated BP nanosheets have been demon

strated as a good PAI agent [97]. As shown in the Fig.8c,

PAI signal was enhanced with the increase of concentra

tion of PEGylated BP nanosheets. PA signals in tumor

sites were strong for several hours following the injection

of PEGylated BP nanosheets, indicating the low tissue-

attenuation coeﬃcient and the prominent accumulation

in tumor focus in comparison with the other organs. In

addition to BP, Tao et al. have developed the uniform

antimonene nanosheets and successfully applied it as PAI

agents in bioimaging [27]. ey reported that the PAI

signal of antimonene nanosheets was stronger than that

of BP nanosheets, which was more suitable for invitro

and in vivo imaging. Recently, other forms of Xenes

including ultrasmall bismuth [98] (2D Bi) nanoparticles

and tellurene [99] (2D Te) nanosheets were also reported

to be ideal candidate for the application in PAI.

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Fig. 8 Emerging Xene-based bioimaging. a NB@BP-based ﬂuorescence imaging (FL) and BP quantum dots based ﬂuorescence imaging

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Gaoetal. J Nanobiotechnol (2021) 19:96

Combining with special computer-aided X-ray technol-

ogy, CT utilizes ionizing radiation to provide 3D images

of biological tissues and ﬁne cross-sections with high

resolution and deep penetration noninvasively. Given

the advantages of long half-life, easy modiﬁcation and

speciﬁc enrichment in tumor region, Xene-based nano

materials also have great potential in the application of

CT imaging. Bismuth possesses good X-ray attenuation

performance, which is relatively cheaper and lower toxic

compared with the conventional CT agents. e edge

value of bismuth (K = 90.5 keV) is three times greater

than that of iodine-based medicine (K = 33.2keV), which

is a common clinic CT agent. erefore, bismuth-based

nanomaterials could maximize the X-ray absorption

eﬃciency and have good CT imaging potential [100].

Lei et al. synthesized ultra-small PVP-coated Bi nano

dots and demonstrated the improved CT imaging results

[101]. e CT imaging resolution is triple as high as that

of the traditional iodine-based contrast agent (Fig.8d).

Liu etal. prepared Bi@Gel (BGPS) and proved that CT

signal was enhanced with the increase of BGPS concen

tration [102]. e Hounsﬁeld unit slope of BGPS is 6.464

Humm

−1

, higher than that of iohexol (4.28 HumM

−1

)

resulting in excellent CT imaging. e obvious CT sig

nals could be detected at the tumor site after injection

for 24h, which further proved that the CT imaging per

formance of BGPS eﬀectively accumulated in the lesion.

In this context, Xene-based nanomaterials are widely

considered as a potential alternative invitro and invivo

imaging. Furthermore, combining these diverse imaging

methods could improve the spatial and temporary sensi

tivity of imaging systems for tumor therapy.

Therapeutic applications

e treatment of the disease, especially targeted therapy,

is essential inclinical medicine [103–106]. Chemotherapy,

photothermal therapy (PTT) and photodynamic therapy

(PDT) are the most common therapeutic methods based

on Xene nanostructures.

PTT is a physical treatment approach to destruct can

cer using local hyperthermia generated by photother-

mal agent with high photothermal conversion eﬃciency.

Xenes with strong absorption in the region of near-

infrared light, has been widely used as photothermal

agents for PTT due to their unique optical performance

[22]. For example, the fatality rate of BP-PEG nanosheets

under 1W/cm

laser irradiation on HeLa cells reached

90%, indicating that BP-PEG nanosheets can promote the

death of cancer cells by good photothermal eﬀect. Invivo

experiments showed that BP-PEG could enhance the

anti-tumor eﬀect through the combination of PTT and

chemotherapy, and no tissue damage was found in the

main organs. Additionally, the photothermal conversion

eﬃciency of Ce6-modiﬁed BP nanosheets were reported

as high as 43.6%. Apart from BP in group VA, 2D anti

mony quantum dots (AM QDs) have been prepared and

functionalized by PEG. e temperature of PEG-coated

AMQDs could increase up to 50 ℃ at the concentra

tion of 200μg/mL, indicating the extremely high pho-

tothermal conversion rate (45.5%). More importantly,

PEG-coated AM QDs could degrade rapidly under the

action of near-infrared light after executing PTT against

tumor. And invivo experiment against MCF-7 indicates

that 2D AM QDs have the best antitumor eﬀect with

out recurrence and obvious side eﬀects induced by local

hyperthermia (Fig. 9a) [26]. It was reported that PVP

encapsulated Bi QDs (PVP-Bi QDs) also exhibited good

photothermal conversion capability under laser irradia

tion of 808nm at the power of 1.3 w/cm

. e temper-

ature of PVP-Bi QDs sharply rose up to 49.5℃ within a

short time, indicating PVP-Bi QDs could rapidly convert

near-infrared light into heat energy. e measured pho

tothermal conversion eﬃciency was about 30%. After

treating U14 tumor with PVP-Bi quantum dots combined

with laser irradiation, the cytotoxicity and eﬀects on nor

mal cells were negligible (Fig. 9b) [102]. As for Group

VIA, Te-based nanomaterials have been proposed to per

form PTT to achieve the purpose of tumor ablation. Yang

and co-workers presented the synthesis of bifunctional

tellurium nanodots, which could not only achieve eﬀec

tive photothermal transformation but also generate ROS

to mediate apoptosis in tumor cells (Fig.9c) [107].

PDT is nowadays another form of phototherapy to

destruct cancer, which possesses the therapeutic proce

dure exerting a selective cytotoxic activity toward malig-

nant cells. In the presence of oxygen, the photosensitizer

or photosensitizing drug could produce reactive oxygen

species (ROS) by irradiation at a certain wavelength cor

responding to an absorbance band of the sensitizer. e

irreversible oxidative damage to the cancer cells in malig

nant tissues is induced by the generated ROS and there

is the minimal normal tissue toxicity. Clinical studies

Fig. 9 Emerging Xene-based therapeutic applications. a Antimonene-based photothermal therapy (PTT). Reprinted with permission [26],

(See ﬁgure on next page.)

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Gaoetal. J Nanobiotechnol (2021) 19:96

have shown that PDT can be curative and signiﬁcantly

improve the reduction of recurrence risk, particularly in

early stage tumors. Various advantages make it a valuable

therapeutic schedule for combination treatments.

Fortunately, Xene-based photosensitizers are expected

to overcome the forementioned limitations. Xene itself

is not only an ideal candidate for PDT but also can

be loaded with photosensitizing drug due to its super

high speciﬁc surface area. Wang etal. reported that BP

nanosheets produced singlet oxygen under 660nm laser

irradiation at the power of 1W/cm

to induce apoptosis

of tumor cells, and the apoptosis rate was 71.5% [108]. As

shown in Fig.9d, e, both invitro and invivo experimen

tal results indicated that the BP nanosheets have great

potential for using as a photosensitizer. Numerous stud

ies show that the synergistic eﬀect of PTT and PDT can

eﬀectively inhibit tumor growth. Yang etal. constructed

a dual functional Ce6-modiﬁed BP nanosheets to real

ize PDT/PTT synergistic treatment [109]. is combi-

nation was endowed with good biocompatibility and

obvious synergistic eﬀect. It was also less-invasive for

normal cells, heart, liver, spleen, kidney and other major

organs. Lin etal. prepared glutathione coated tellurium

nanosheets (Te@GSH), which showed a noteworthy PDT

capability with a high quantum yield about 0.91 of singlet

oxygen (

) under 670nm light irradiation (Fig.9f, g)

[98]. Te@GSH could produce

and eﬀectively inhibit

the growth of tumor cells. Hematoxylin–eosin (H&E)

staining images showed that the tumor sections in the

Te@GSH light group were seriously damaged, while the

morphology of other cells was normal and the physi

ological morphology of the viscera was not changed. Te@

GSH was further proved a safe and reliable PDT agent.

In addition to the two-dimensional Xenes materials men

tioned above, the applications of BP QDs and tellurium

nanoparticles in PDT have also been reported.

Although there are some drawbacks, chemotherapy

is still the main method for cancer therapy in clinical

present. e satisfying chemotherapy eﬀect could be

achieved via combining 2D Xenes with anticancer func

tional drug. 2D Xenes have unique lamellar structure,

adjustable atomic layer thickness, large speciﬁc surface

area and easy surface functionalization. ese advantages

provide an important basis for high drug loading and

eﬀective drug delivery [28, 110]. As a newly developed

2D material, BP nanosheets are metal-free layered semi

conductors with variable band gap, high surface reactiv-

ity, strong biodegradability, large speciﬁc surface area,

which can eﬃciently load drug molecules, antibodies

and biological molecules. erefore, combining anticar

cinogen with BP nanosheets is an eﬀective approach for

chemotherapy. For example, Chen and co-workers pre

sented the synthesis of a multifunctional system, which

combined BP nanosheets and lipophilic drugs (doxo

rubicin, DOX) through electrostatic eﬀect (Fig. 10a, b)

[111]. e loading capacity of DOX reached up to 950%,

which was much higher than the drug loading of con

ventional deliveries reported previously. More impor-

tantly, the release rate of the drug at pH 5 was 6 times

higher than that at pH 7, demonstrating that the drug

was beneﬁcial to release at a lower pH and the release

proﬁle was pH-dependent. Because of the acidic tumor

microenvironment, BP-DOX is favorable for drug release

within the tumor. BP has photothermal eﬀect, which can

further promote the release of DOX. Under the irradia

tion of 808nm laser, the release rate of DOX was up to

90%. In addition to DOX, chloroquine (CQ) has also

been successfully loaded onto BP nanosheets [112]. e

BP nanosheets loaded with CQ enter the cell lysosomes,

realizing the synergistic treatment of photothermal ther

apy and chemotherapy, which signiﬁcantly improved

the therapeutic eﬀect of cancer. Following these studies,

Zeng group employed polydopamine (PDA) to inno

vate a facile and low-cost surface modiﬁcation strat-

egy to endow BP nanosheets with good water-solubility

and bio-compatibility (Fig.10c, d) [113]. DOX and P-gp

siRNA physically adsorbed on the surface of PDA coated

BP-based drug delivery for multidrug resistant cancer

treatment. e release rate of DOX and P-gp siRNA

could be eﬀectively controlled by adjusting pH and near

infrared laser irradiation. In vivo experiments showed

that the system could successfully introduce drugs into

tumor cells, and exhibited a signiﬁcant synergistic ther

apeutic eﬀect on multidrug resistant breast cancer. In a

word, by constructing a PDA-modiﬁed BP nanosheets

multifunctional drug delivery platform, the water-solu

bility, bio-compatibility and photothermal performance

could be improved. It could not only achieve selective cell

targeting, but also show eﬀective inhibition of tumor cell

proliferation through multi-mode combination therapy.

e multifunctional drug delivery system provides

a new direction for targeted chemotherapy and gene

therapy for multidrug resistant cancers. Tao et al. has

reported the coating of antimony nanosheets (2D Sb)

multifunctional system with amphiphilic PEG polymer

for targeted delivery of chemotherapy drugs and photo

thermal therapy [27]. As illustrated in Fig.10e, f, anti-

mony nanosheets were encapsulated by PEG grafted

amphiphilic polymer to oﬀer a "hydrophobic arm" with

the feasibility of physically absorbance "catching" lipo

philic drugs (DOX) by hydrophobic interaction. e

obtained drug loading capacity was about 150% (weight

ratio) and the measured drug release rate was 69.8%

at pH 5 under the near-infrared irradiation. AM-PEG/

DOX has deep photoinduced penetration and excellent

photothermal conversion capability. e apoptosis rate

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Gaoetal. J Nanobiotechnol (2021) 19:96

of MCF-7 cells was about 91.5% and the tumor growth

inhibition rate (TGI) of this strategy reached 98.1%,

which was signiﬁcantly higher than that of monotherapy.

It was the ﬁrst time to report the photon drug delivery

platform of 2D Sb nanosheets, which may indicate a new

starting point in cancer treatment research. Apparently,

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Gaoetal. J Nanobiotechnol (2021) 19:96

Xenes as drug delivery have attracted extensive attention

and made rapid progress in research. Although there are

still huge challenges, it is believed that in the near future,

Xenes will make great breakthroughs and realize clinical

applications.

Antibacterial

Bacterial infection is a process in which bacteria invade

and cause local or systemic damage to the host, thus

showing its pathogenicity and inducing the occurrence

of disease. Currently, the most common treatment for

bacterial infections is antibiotic therapy. However, due

to the emergence of multi-drug resistant superbugs, tra

ditional antibiotics are no longer able to solve the arisen

problem of bacterial infection. An overuse of antibiotics

has further accelerated the creation of antibiotic-resist

ant germs [114, 115]. To date, tremendous eﬀorts have

been devoted to settle the awful bacterial drug resist

ance. Xenes have good membrane permeability, excel-

lent biocompatibility, large speciﬁc surface area and easy

surface modiﬁcation, so they can interact with bacterial

membranes better and improve antibacterial eﬀect dis

tinctly. At present, great progress has been made in the

development of Xenes based antibacterial agents [29, 30].

For instance, Sun etal. employed BP nanosheets as an

antibacterial agent to against gram-negative escherichia

coli (E. coli) and gram-positive staphylococcus aureus (S.

aureas) by means of 808nm irradiation [116]. e steri

lization rate was as high as 99.2%, far higher than that of

graphene and 2D MoS

, showing signiﬁcant antibacterial

ability (Fig.11a). e eﬀect of BP nanosheets on staphy

lococcus aureus were slightly larger than that of E.coli,

which may be related to the diﬀerent microstructure of

diﬀerent cell wall. Within a certain concentration range,

the bacterial lethality improved and the cytotoxicity

would be negligible with the increasing of BP concentra

tion, indicating the good biocompatibility and the great

potential in antibiotic area. Ouyang’ group constructed

a novel Ag@BP nanostructure on the substrate of BP

nanosheets [117]. Under near-infrared light, BP substrate

has excellent photothermal eﬀect and can rapidly destroy

bacterial membrane. Synergistically Ag

was released

slowly by oxidative dissolution mechanism to inhibit the

proliferation of bacteria. ey demonstrated that higher

amounts of methicillin-resistant staphylococcus aureus

(MRSA) death (93%) caused by Ag@BP than BP alone.

After treatment with Ag@BP, the skin tissue was intact

and the inﬂammation was eﬀectively inhibited. e anti

bacterial eﬀect of Ag@BP is mediated by local high tem-

perature and oxidative stress, and has nothing to do with

the structure of bacteria, thus avoiding the occurrence of

drug-resistant bacteria. Ag@BP have good biocompat

ibility and biosafety making them have great potential

in clinical application in the future. is work also laid

a foundation for the treatment of drug-resistant bacte

ria based on two-dimensional semiconductor and other

antibacterial material microspheres. Zhang etal. directly

synthesized a new type of copper-carrying (BP/Cu) nano

composite by one-step reduction method, and studied its

antibacterial mechanism (Fig.11b–f) [118]. Active lone

pair electrons could allodially transfer from BP to the sur

face of metal according to the invivo experiments. e

interaction between BP and copper leads to the increase

of ROS production mainly including hydroxyl radicals

and superoxide anion. e generated ROS active species

could directly damage the cell membrane, phospholipid

or membrane protein, thereby destroying the bacterial

structure and further inducing bacterial death.

In addition to BP, antimony nanosheets have great

potential for synergistic antibacterial applications. Liu

etal. introduced antimony nanosheets into the center

of chitosan (CS) network to construct a composite

hydrogel (CS/AM-NSs hydrogel) with excellent anti

bacterial properties (Fig.11g–i) [119]. e interaction

between CS and bacterial membrane made the bacte

ria accumulate on the surface of the composite hydro-

gel. e bactericidal property of the composite could

kill most bacteria, and the photothermal properties of

the antimony nanosheets could eliminate the residual

bacteria. e antibacterial test results invitro showed

that the killing rate of CS/AM-NSS0.8 hydrogel against

E.coli and S. aureus was 97.1% and 100%, respectively.

e results showed that the synergistic eﬀect of CS,

AM-NSs and PTT could eﬀectively kill bacteria and

further promote wound healing. ere was no obvi

ous inﬂammation, injury or necrosis, no aggregation of

materials in major tissues and organs, and the toxicity

was relatively weak in vivo. e material is expected

to be widely used in bandages to treat bacterial wound

infections. 2D antimony based nanomaterials was used

in antimicrobial therapy for the ﬁrst time, providing

a future direction of biomedical applications for 2D

Fig. 11 Emerging Xene-based antimicrobial application. a Phosphorene-based antimicrobial application. Reprinted with permission [115],

infection. h, i Pictures of antibacterial eﬀect in vitro and photographic images and tissue sections of wounds treated by Staphylococcus aureus

(See ﬁgure on next page.)

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Gaoetal. J Nanobiotechnol (2021) 19:96

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Gaoetal. J Nanobiotechnol (2021) 19:96

Xenes. Rangrazi et al. synthesized chitosan groomed

selenium nanoparticles (CTS-Se NPs) directly by a sim

ple chemical reduction method with ascorbic acid as

reducing agent [120]. e results showed that CTS-Se

NPs exhibited obvious bactericidal eﬀect on gram-pos

itive bacteria, streptococcus sanguis, staphylococcus

aureus and enterococcus faecalis even at extremely

low concentration of CTS-Se NPs. Moreover, this sys

tem had no obvious inhibitory eﬀect on gram-positive

pseudomonas aeruginosa and salmonella typhimurium,

which indicated that it possessed selective antibacterial

function. CTS-Se NPs have great reference and applica

tion value in medical ﬁeld such as forehead sterilization

of medical devices and mouthwash for dental diseases.

In brief, 2D Xenes are conducive to contact with bac

teria and penetrate the cell membrane due to their

internal features containing high speciﬁc surface area,

light-induced ROS production, outstanding photother

mal conversion eﬃciency.

Conclusion andprospect

In this review, we summarized the recent developments

in 2D Xenes (group VA and group VIA) in terms of

design, synthesis and biomedical applications. Numer

ous typical examples were enumerated to demonstrate

the various aspects of 2D Xenes in detail. Admittedly,

the research of 2D Xenes has made substantial advances

in recent years, however, several technical challenges

remain, which impose barriers to their practical appli

cations. On one hand, controllable preparation of 2D

Xenes is of primary importance, including morphology,

composition and adjustable surface properties. ere is

no standard method to synthesize 2D Xenes and how to

prepare 2D Xenes on a large scale is still a huge challenge.

erefore, more profound understanding still needs to be

explored in future. On another hand, an urgent task is to

pinpoint the biosecurity of 2D Xenes including the accu

mulation, the accurate retention time in the lesion and

the actual clearance mechanism. 2D Xenes are ingested,

the prognosis within the body and the generated eﬀect

on nervous and immune system still needs to be further

systematic studied. erefore, further nanotoxicology

and pharmacokinetics studies on 2D Xene-based thera

nostic platform should be carefully conﬁrmed.

In conclusion, 2D Xenes are facing unprecedented

challenges and opportunities in biomedical ﬁelds. e

realization of theoretical knowledge and clinical appli

cations of 2D Xenes nanomaterials requires the joint

eﬀorts of all researchers. It is believed that with the con

tinuous development of nanotechnology, 2D Xenes will

be applied in a variety of biomedical ﬁelds in the near

future.

Abbreviations

2D: Two-dimensional; Xenes: Monoelemental nanomaterials; TMD: Transition

metal dihalide; h-BN: Hexagonal boron nitride; g-C

: Graphite phase nitro-

gen carbide; MoS

: Molybdenum disulﬁde; LRH: Layered rare earth hydroxide;

LDH: Layered double hydride; CT: Computed tomography; PAI: Photoacoustic

imaging; FI: Fluorescence imaging; PTT: Photothermal therapy; PDT: Photo-

dynamic therapy; TEM: Transmission electron microscopy; AFM: Atomic force

microscope; CHP: N-cyclohexyl-2-pyrrolidone; DMF: Dimethylformamide;

DMSO: Dimethylsulfoxide; IPA: Isopropyl alcohol; NMP: N-methyl-pyrrolidone;

QDs: Quantum dots; DSPE-mPEG: 1,2-Distearoyl-sn-glycero-3-phosphoethan-

olamine-N-[methoxy (poly ethylene glycol)]; NH

: Ammonium hexaﬂuoro-

phosphate; MBE: Molecular beam epitaxy; CVD: Chemical vapor deposition;

HRSTM: High resolution scanning tunneling microscopy; Na

TeO

: Sodium

tellurite; N

·H

O: Hydrazine hydrate; NB: Nile blue; FITC: Fluoresce in isothio-

cyanate; ROS: Reactive oxygen species; Te@GSH: Glutathione coated tellurium

nanosheets; H&E: Hematoxylin–eosin; TGI: Tumor growth inhibition rate; E. coli:

Escherichia coli; S. aureas: Staphylococcus aureus; MRSA: Methicillin-resistant

staphylococcus aureus; CS: Chitosan.

Authors’ contributions

PG and YX wrote the main draft under LL and WL’s supervision. YW helped in

paper writing, WT helped in ﬁnal editing. All authors read and approved the

ﬁnal manuscript.

Funding

Financial support by National Natural Science Foundation of China (No.

21871246; to LL), the Grant of Jilin Province Science & Technology Committee

(No. 20180101194JC and 20200201082JC; to LL and WL), the Science & Tech-

nology Innovation and Development projects of Jilin city (No. 20190601178;

to WL), Jilin Province Education Department the Science & Technology

development project (No. JJKH20200741KJ and JJKH20200449KJ; to LL and

WL) are acknowledged.

Availability of data and materials

Not applicable.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Author details

School of Chemistry and Environmental Engineering, Changchun University

of Science and Technology, Changchun 130022, China.

Center for Nanomed-

icine and Department of Anesthesiology, Brigham and Women’s Hospital, Har-

vard Medical School, Boston, MA 02115, USA.

Jilin Collaborative Innovation

Center for Antibody Engineering, Jilin Medical University, Jilin 132013, China.

Received: 15 January 2021 Accepted: 6 March 2021

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